Connective tissue diseases: A focus on lupus and sclerosing disorders Alisa Femia, MD Assistant Professor Director of Inpatient Dermatology Ronald O. Perelman Department of Dermatology New York University School of Medicine September 23, 2016 1

Disclosures The content of this presentation does not relate to any product of a commercial interest; therefore, there are no relevant financial relationships to disclose This presentation includes discussion of off-label use of medications

Case 1

Acute Cutaneous Lupus Erythematosus (ACLE) Often confused with: Erythrotelangiectatic rosacea Seborrheic dermatitis Dermatomyositis Drug or viral eruption (especially when generalized) Broader Ddx: Contact dermatitis, flushing disorders

Acute Cutaneous Lupus Erythematosus (ACLE) Clinical Clues: Spares the nasolabial folds Often associated alopecia, particularly of the frontal scalp May have peri-oral hemorrhagic crusting Relatively fixed Generalized ACLE often involves areas that are protected from the sun

Acute Cutaneous Lupus Erythematosus (ACLE) What percentage of patients with the “butterfly rash” have or will develop SLE?

Acute Cutaneous Lupus Erythematosus (ACLE) What percentage of patients with the “butterfly rash” have or will develop SLE? Virtually 100%

Acute Cutaneous Lupus Erythematosus (ACLE) What percentage of patients with the “butterfly rash” have or will develop SLE? Virtually 100% May occur prior to symptoms of SLE Flares tend to parallel SLE activity

Pearls Malar rash has characteristic clinical features Generalized acute cutaneous lupus can involve non-photoexposed sites Associated with SLE in virtually 100%

Case 2

Discoid Lupus Erythematosus PASTED P – follicular Plugging A – atrophy S – scale T – telangiectasia E – erythema D - dyspigmentation

Discoid Lupus Erythematosus PASTED P – follicular Plugging A – atrophy S – scale T – telangiectasia E – erythema D - dyspigmentation

43 patients with CLE treated with MTX 31 refractory to anti-malarials 12 refractory to additional agents Improvement in 98%

Therapeutic Ladder Photoprotection Smoking cessation Topicals, intralesional triamcinolone

Therapeutic Ladder Photoprotection, smoking cessation, local therapy Antimalarial therapy Alone or in combination

Antimalarials Hydroxychloroquine Chloroquine

Antimalarials Hydroxychloroquine Chloroquine Quinacrine

Therapeutic Ladder Photoprotection, smoking cessation, local therapy Antimalarial therapy Methotrexate

Therapeutic Ladder Photoprotection, smoking cessation, local therapy Antimalarial therapy Methotrexate Mycophenolate mofetil, belimumab, azathioprine, IVIG, acitretin/isotretinoin, dapsone, thalidomide, lenalinomide

Therapeutic Ladder Photoprotection, smoking cessation, local therapy Antimalarial therapy Methotrexate Mycophenolate mofetil, belimumab, azathioprine, IVIG, acitretin/isotretinoin, dapsone, thalidomide, lenalinomide

Therapeutic Ladder Photoprotection, smoking cessation, local therapy Antimalarial therapy Methotrexate Mycophenolate mofetil, belimumab, azathioprine, IVIG, acitretin/isotretinoin, dapsone, thalidomide, lenalinomide

Thalidomide R.E.M.S (Risk Evaluation and Mitigation Strategy) program Prescriber and pharmacy certify with Celgene REMS program Patients sign a patient-physician agreement form Pregnancy testing for women Present in semen of males

Discoid lupus erythematosus (DLE) What percentage of patients will be ANA positive?

Discoid lupus erythematosus (DLE) What percentage of patients will be ANA positive? Roughly 35%

Discoid lupus erythematosus (DLE) How many patients with DLE will develop SLE?

Risk of subsequent diagnosis of SLE in DLE patients = 17% 27

Discoid lupus erythematosus (DLE) How many patients with DLE will develop SLE? Roughly 15-20%

ç DLE in children less common than in adults Equal sex distribution prior to puberty Higher progression to SLE

Pearls DLE is scarring, treat early Higher risk of progression to SLE than previously thought Low threshold for antimalarials Often require escalation beyond antimalarials

Case 3

Chronic Cutaneous Lupus Suspect lupus panniculitis with any substantial contour change Involves fatty areas (cheeks, upper outer arms, hips, thighs) Lupus profundus = DLE overlying lupus panniculitis

Lupus Panniculitis Erythema Nodosum Face, upper outer arms, hips, thighs Lobular panniculitis Permanent contour change Chronic Anterior lower legs Septal panniculitis Non-scarring Usually self-resolving

Lupus Mastitis Carducci M, et al. J Eur Acad Dermatol Venereol. 2005;19(2):260-2. Dandinoglu T, et al. Orthop Muscul Syst. 2014;3(1). Fernández-Torres R, et al. J Am Acad Dermatol. 2009;60(6):1074-6. Rosa M, et al. Ann Diagn Pathol. 2013;17(2):230-3.

Pearls Lupus panniculitis is a scarring lobular panniculitis Can affect the breasts as well (mimics malignancy) Consider filler therapy only once disease quiescence has been ascertained

Case 4

SQ panniculitis-like T-cell lymphoma Rare TCL with predilection for SQ tissue Can clinically and histologically mimic lupus panniculitis 19% have associated autoimmune disease Most commonly SLE

Diffuse MxA staining correlated with LEP Endothelial staining also correlated with LEP Minimal MxA staining correlated with SPTCL

Pearls Maintain high suspicion for LEP that fails to respond to therapy -> incisional biopsy SPTL often associated with autoimmune disease

Case 5

Subacute Cutaneous Lupus Approximately 50% associated with SLE Anti-Ro positive 60-90%, highly photo-sensitive! Heals with dyspigmentation, not scarring

Approximately 30% of SCLE cases are drug-induced Terbinafine, HCTZ, proton-pump inhibitors Anti-TNF-α

Neonatal Lupus Skin involvement most frequent manifestation Cardiac involvement in roughly 65% Hepatobiliary, hematologic involvement

63% required pacemakers 19% mortality 82% detected prior to 30 weeks gestational age

Pearls Subacute cutaneous lupus is highly photosensitive Psoriasiform and annular subtypes Anti-Ro positive patients must obtain fetal echocardiograms

Case 6

Pediatric Morphea AKA “localized scleroderma” Linear morphea is most common variant Often involves deeper structures Risk for permanent contractures and functional disability Often lacks erythema – do not undertreat!

Linear morphea: 52% Undergrowth of the extremity: 33% Contractures: 26%

56% with permanent sequelae Limited range of motion Deep atrophy Limb-length discrepancy Joint contractures

Extremity Linear Morphea: Therapy Topical therapy: 55 55

Extremity Linear Morphea: Therapy Topical therapy: Only adjunctive, not used alone 56 56

Extremity Linear Morphea: Therapy Overlying a joint and/or changing rapidly: MTX 1mg/kg (up to 25mg/week) Prednisone 1mg/kg, ~3-6 months taper Not overlying joint: Consider MTX without prednisone Second line: Mycophenolate mofetil (adults 1.5gm BID, children 600mg/m2 BID) 57 57

Craniofacial Morphea Includes “Parry-Romberg” Syndrome, en coup de sabre (ECDS) Potential sequelae Neurologic, ophthalmologic, dental Cosmetic disfigurement

Therapy: Craniofacial Morphea/PHA IV methylprednisolone 30mg/kg qweekly x 12 weeks MTX 1 mg/kg/week (up to 25mg/week) Often given IV along with methylprednisolone Second line if fail MTX is mycophenolate mofetil Topicals only adjunctive 59 59

Pearls Linear morphea of the extremities is associated with functional limitation, treatment with methotrexate +/- prednisone Craniofacial morphea is associated with severe disfigurement, treatment with IV methylprednisolone + methotrexate

Pearls Hemifacial atrophy may present with early inflammatory erythema mimicking port-wine stain Atrophy appears worse as child grows even once disease quiescent, counseling at onset is imperative Aggressive therapy necessary to limit disfigurement

Case 7

Adult-onset Linear Morphea 61 patients Mean delay in diagnosis 27 months 44% functional limitations Severe cosmetic disfigurement

Adult-onset Linear Morphea With methotrexate: Resolution more likely (29% vs. 4%) Progression and recurrence less likely

Pearls Functional limitations are common with adult-onset linear morphea Treatment algorithm similar to pediatric-onset morphea

Case 8

Systemic Sclerosis “Puffy hand” sign is often earliest clue Look for Raynaud’s and nailfold capillary changes

Phosphodiesterase inhibitors, Treatment options Immuno- modulators Vascular modulators Anti-fibrotic medications Cyclophosphamide Corticosteroids MTX MMF IVIG, etc. CCB’s ACE-I’s Phosphodiesterase inhibitors, etc. D-penicillamine Imatinib ECP Phototherapy

25 patients with recent onset diffuse cutaneous systemic sclerosis Statistically significant decrease in modified Rodnan Skin Score and Body Surface Area of involvement Slow onset – typically still with worsening for 6 months PFT’s stabilized

Eosinophilic Fasciitis Edema, tightening of extremities Often confused with systemic sclerosis but distinguish by lack of distal fingertip involvement, nailfold capillary changes Raynaud’s also typically absent

Evaluated prednisone monotherapy, hydroxychloroquine(HCL) monotherapy, and combination therapy 25 had partial to complete response to prednisone, 6 to HCL monotherapy, and 4 to combination therapy

Retrospective review between 1995 and 2014 at three academic centers 1,626 patients, 63 with confirmed eosinophilic fasciitis

Pearls Clinical history and physical examination will help distinguish SSc and EF Early diagnosis and intervention essential MMF may be helpful for cutaneous involvement in SSc Systemic steroids + MTX seems to improve patient outcomes in EF

Thank you!